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Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

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ClinicalTrials.gov Identifier: NCT00729924
Recruitment Status : Completed
First Posted : August 8, 2008
Results First Posted : March 3, 2015
Last Update Posted : March 3, 2015
Sponsor:
Information provided by (Responsible Party):
David Haas, Vanderbilt University

Study Description
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Brief Summary:
This study is being done to find out how much of the drug raltegravir (RGV) gets into cerebrospinal fluid (CSF), compared to how much get into the blood and to find out if normal changes in a certain gene in your body affects how much RGV gets into the CSF.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Raltegravir Phase 2 Phase 3

Detailed Description:
The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in the blood-brain barrier where it limits entry of substrate drugs into the central nervous system. Raltegravir (MK-0158), a new HIV-1 integrase inhibitor and potentially major addition to the therapeutic armamentarium against HIV, is a substrate for P-gp. Studies are warranted to elucidate the relevance of P-gp transport for raltegravir in the central nervous system.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid
Study Start Date : August 2008
Actual Primary Completion Date : February 2011
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Open label oral raltegravir
Raltegravir a single 400 mg pill taken orally every 12 hours for a total of 7 days.
 Drug: Raltegravir
400mg orally every 12 hours for 7 days
Other Name: MK-0518


Outcome Measures
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Primary Outcome Measures :
  1. Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Plasma Area-under-the-curve. [ Time Frame: Day 7 ]
    The primary outcome for this study was the ratio of the 4-hour CSF concentration value (ng/mL) to the partial plasma area-under-the-curve 0-4h value (h*ng/mL).


Secondary Outcome Measures :
  1. Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Single Plasma Timepoint. [ Time Frame: Day 7 ]
    This outcome was the ratio of the 4-hour CSF concentration value (ng/mL) to the 4-hour plasma concentration value (ng/mL).


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  1. Able to give informed consent.
  2. Negative HIV-1 serology.
  3. At least 18 but no more than 55 years of age.
  4. Body mass index <30.
  5. Estimated creatinine clearance ≥ 50 mL/minute within 30 days prior to study entry.

  6. Within 30 days prior to study entry:

    • Absolute neutrophil count ≥ 1,000/mm3.
    • Hemoglobin ≥ 12.5 g/dL for males and ≥ 11.5 g/dL for females.
    • Platelet count ≥ 100,000/mm3.
    • AST, ALT, and total bilirubin within normal range.
    • Alkaline phosphatase < or = 1.5 x upper limit of normal.
  7. Female study volunteers of reproductive potential must have a negative serum or urine pregnancy test performed within 30 days before study entry.
  8. Must agree not to participate in a conception process.
  9. Drug transporter gene ABCB1 position 3435 genotype C/C or T/T.

Exclusion criteria:

  1. Use of any medication that is metabolized by CYP3A or UGT1A1.
  2. Anticipated need to take any medication that is metabolized by CYP3A or UGT1A1 during the study.
  3. Active drug use or dependence.
  4. Inability to abstain from alcohol-containing beverages, grapefruit, and grapefruit juice.
  5. Serious illness that would interfere with study participation.
  6. Hospitalization for any reason or therapy for serious illness within 14 days prior to study entry.
  7. History of hypersensitivity to study drug or its formulation.
  8. As determined by the investigator, a significant active or previous history of cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease(s). This is inclusive of chronic illnesses such as hypertension, coronary artery disease, arthritis, diabetes, any chronic gastrointestinal conditions that may affect drug absorption, etc.
  9. Breast-feeding.
  10. Evidence of CNS infection or space occupying lesion by history or physical examination.
  11. History of significant CNS disorder.
  12. Prisoners or subjects who are compulsorily detained.
  13. ABCB1 position 3435 C/T heterozygosity.
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00729924


Locations
United States, Tennessee
Vanderbilt Therapeutics Clinical Research Site
Nashville, Tennessee, United States, 37204
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: David W Haas, MD Vanderbilt University Medical Center
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Responsible Party: David Haas, Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00729924     History of Changes
Other Study ID Numbers: 080536
First Posted: August 8, 2008    Key Record Dates
Results First Posted: March 3, 2015
Last Update Posted: March 3, 2015
Last Verified: March 2015

Keywords provided by David Haas, Vanderbilt University:
Raltegravir
CSF
ABCB1 SNP
HIV/AIDS

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
 Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action